We will establish a center to promote the study of cardiovascular diseases in South Carolina. Our COBRE focus on cardiovascular disease is significant because the citizens of our state are more prone to cardiovascular disease than anywhere else in the nation. For this reason, the two medical schools in the state have united to develop the South Carolina COBRE on Cardiovascular Disease. This COME will significantly augment joint efforts in South Carolina to recruit, train and retain a critical mass of investigators with multidisciplinary skills and adequate infrastructure to: (1) collaborate effectively in fundamental mechanistic studies of cardiovascular diseases, and (2) compete successfully at the national level for NIH and other merit-reviewed funding required to support and extend their research endeavors. Five scientific projects proposed by talented, newly recruited tenure-track faculty from five different departments, three high tech scientific cores (transgenics, imaging, microarray/proteomics) directed by outstanding investigators with proven track records in their area of expertise and an administrative/mentoring core comprise the proposed center. The overarching theme is that cardiovascular diseases derive from final common pathogenic pathways: proliferation, remodeling, apoptosis, transdifferentiation and vasculogenesis, each of which is the focus of one or more projects. While the thematic focus is cardiovascular, the operant theme for implementation is mentoring. In states that are less competitive for research funding at the national level, effective mentoring of new investigators is an essential element of a research development plan. This proposal addresses this need directly by: (1) pairing targeted investigators with established NIH-funded researchers who have exceptional mentoring track records as well as relevant critical expertise; (2) developing structured activities for skills acquisition and enhancement, such as seminars, journal clubs, retreats and special courses; (3) guaranteeing access to essential core resources with sufficient scientific expertise and technical support to optimize their use; and (4) implementing a regular schedule (checkpoints) of progress reports and evaluation with critical assistance from an External Advisory Committee of nationally recognized scientists.